Novel alpha-hydrazononitriles from 4-cyanoformimidoyl-5-aminoimidazoles and hydrazines: characterization and isomerization

Abstract

Imidazole derivatives are attractive building blocks in chemical synthesis and drug discovery, because they are key components in many bioactive compounds.1 4-Substituted 5-aminoimidazoles are important biosynthetic intermediates in nature, but reports on the chemistry of 5-aminoimidazoles in the literature are limited due to their known instability.2 Arylhydrazononitriles have been used as key synthons for the preparation of a wide variety and uniquely substituted heterocyclic substances.3 Additionally, the results of biological evaluations demonstrated that members of this class of compounds have promising antimicrobial activities against Gram negative bacteria, Gram positive bacteria and Yeast. In our research group, 4-substituted 5-aminoimidazoles are easily obtained from accessible reagents by an efficient method. Studies on the condensation of 4-cyanoformimidoyl 5-aminoimidazole precursors with hydrazines showed that this reaction generated novel α-phenylhydrazononitriles 1 under mild experimental conditions. These results prompted us to prepare additional series of new analogues incorporating diverse hydrazonoyl moieties, in order to study their antifungal activities. A selection of the target molecules 1 was obtained in moderate-good yield and their structures were well established by IR and NMR spectroscopy. The chemical stability of the obtained α-phenylhydrazononitriles 1 was investigated and an easy evolution to a similar product was detected by 1 H NMR when compounds having R=H were maintained in solution at room temperature. The structures of isomers 2 were assigned to the final products with the aid of 13C and 2D NMR and the NOE techniques. In order to investigate this isomerization, kinetic studies were performed by 1 H NMR and will be presented.